Prognostication for patients with cancer is important for clinical planning and management, but remains challenging given the large number of factors that can influence outcomes. As such, there is a ...need to identify features that can robustly predict patient outcomes. We evaluated 8608 patient tumor samples across 16 cancer types from The Cancer Genome Atlas and generated distinct survival classifiers for each using clinical and histopathological data accessible to standard oncology workflows. For cancers that had poor model performance, we deployed a random-forest-embedded sequential forward selection approach that began with an initial subset of the 15 most predictive clinicopathological features before sequentially appending the next most informative gene as an additional feature. With classifiers derived from clinical and histopathological features alone, we observed cancer-type-dependent model performance and an area under the receiver operating curve (AUROC) range of 0.65 to 0.91 across all 16 cancer types for 1- and 3-year survival prediction, with some classifiers consistently outperforming those for others. As such, for cancers that had poor model performance, we posited that the addition of more complex biomolecular features could enhance our ability to prognose patients where clinicopathological features were insufficient. With the inclusion of gene expression data, model performance for 3 select cancers (glioblastoma, stomach/gastric adenocarcinoma, ovarian serous carcinoma) markedly increased from initial AUROC scores of 0.66, 0.69, and 0.67 to 0.76, 0.77, and 0.77, respectively. As a whole, this study provides a thorough examination of the relative contributions of clinical, pathological, and gene expression data in predicting overall survival and reveals cancer types for which clinical features are already strong predictors and those where additional biomolecular information is needed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Selective downregulation of the human antigen R (HuR) protein by siRNA may provide a powerful approach for treating lung cancer. To this end, we investigated the efficacy of transferrin ...receptor-targeted liposomal nanoparticle-based HuR siRNA (HuR-TfNP) therapy and compared with control siRNA (C)-TfNP therapy both,
and
using lung cancer models.
studies showed HuR-TfNP, but not C-TfNP, efficiently downregulated HuR and HuR-regulated proteins in A549, and HCC827 lung cancer cells, resulting in reduced cell viability, inhibition of cell migration and invasion, and induction of G
cell-cycle arrest culminating in apoptosis. However, HuR-TfNP activity in normal MRC-9 lung fibroblasts was negligible.
biodistribution study demonstrated that fluorescently labeled HuR-siRNA or ICG dye-loaded TfNP localized in tumor tissues. Efficacy studies showed intratumoral or intravenous administration of HuR-TfNP significantly inhibited A549 (>55% inhibition) and HCC827 (>45% inhibition) subcutaneous tumor growth compared with C-TfNP. Furthermore, HuR-TfNP treatment reduced HuR, Ki67, and CD31 expression and increased caspase-9 and PARP cleavage and TUNEL-positive staining indicative of apoptotic cell death in tumor tissues compared with C-TfNP treatment. The antitumor activity of HuR-TfNP was also observed in an A549-luc lung metastatic model, as significantly fewer tumor nodules (9.5 ± 3.1;
< 0.001; 88% inhibition) were observed in HuR-TfNP-treated group compared with the C-TfNP-treated group (77.7 ± 20.1). Significant reduction in HuR, Ki67, and CD31 expression was also observed in the tumor tissues of HuR-TfNP-treatment compared with C-TfNP treatment. Our findings highlight HuR-TfNP as a promising nanotherapeutic system for lung cancer treatment.
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This study is motivated by the fact that there are currently no widely used applications available to quantitatively measure a power wheelchair user's mobility, which is an important indicator of ...quality of life. To address this issue, we propose an approach that allows power wheelchair users to use their own mobile devices, e.g., a smartphone or smartwatch, to non-intrusively collect mobility data in their daily life. However, the convenience of data collection brings substantial challenges in data analysis because the data patterns associated with wheelchair maneuvers are not as strong as other activities, e.g., walking, running, etc. In addition, the built-in sensors in different mobile devices create significant heterogeneity in terms of sensitivity, noise patterns, sampling settings, etc. To address the aforementioned challenges, we developed a novel approach composed of algorithms that work collaboratively to reduce noise, identify patterns intrinsic to wheelchair maneuvers, and finalize mobility analysis by removing spikes and dips caused by abrupt maneuver changes. We conducted a series of experiments to evaluate the proposed approach. Experimental results showed that our approach could accurately determine wheelchair maneuvers regardless of the models and placements of the mobile devices.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Recent investigations have demonstrated that polyphenolic catechins inhibit cancer cell proliferation and tumor growth. However, how the major active component of tea catechins, epigallocatechin-3 ...gallate (EGCG), mediates anticancerous effects has not been extensively examined. We have investigated the cell growth inhibitory effects of EGCG on cell growth of the human breast cancer cell line MCF-7, and the mechanism of its action with emphasis on the regulation of tumor cell survival. A significant EGCG dose-dependent growth inhibition was observed coordinated with EGCG-induced apoptosis. Analysis of survivin expression after addition of EGCG showed that both survivin mRNA and protein were decreased. The survivin-promoter luciferase activity in EGCG-treated cells was significantly inhibited by 91+/-2.0% (P<0.001), compared with the control. Interestingly, EGCG strongly inhibited the basal activation of phospho-AKT and AKT kinase activity as early as 30 min after treatment. Furthermore, inhibition of AKT kinase activity by EGCG preceded the suppression of survivin (1 h post treatment), followed by increased caspase-9 activity (6 h post treatment). A dominant negative AKT or the phosphatidylinositol 3-kinase inhibitor, LY294002, also strongly inhibited survivin promoter activity, providing further evidence to support the hypothesis that the inhibitory effect of EGCG on survivin is mediated via the AKT pathway. Therefore, EGCG is a potent proapoptotic agent in MCF-7 breast cancer cells that targets survivin expression via suppression of the AKT pathway.
Marine environmental design parameter extrapolation has important applications in marine engineering and coastal disaster prevention. The distribution models used for environmental design parameter ...usually pass the hypothesis tests in statistical analysis, but the calculation results of different distribution models often vary largely. In this paper, based on the information entropy, the overall uncertainty test criteria were studied for commonly used distributions including Gumbel, Weibull, and Pearson-III distribution. An improved method for parameter estimation of the maximum entropy distribution model is proposed on the basis of moment estimation. The study in this paper shows that the number of sample data and the degree of dispersion are proportional to the information entropy, and the overall uncertainty of the maximum entropy distribution model is minimal compared with other models.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Typhoon storm surge disasters are one of the main restrictive factors of sustainable development in coastal areas. They are one of several important tasks in disaster prevention and reduction in ...coastal areas and require reasonable and accurate calculations of wave height in typhoon-affected sea areas to predict and resist typhoon storm surge disasters. In this paper, the design wave height estimation method based on the stochastic process and the principle of maximum entropy are theoretically advanced, and it can provide a new idea as well as a new method for the estimation of the return level for marine environmental elements under the influence of extreme weather. The model uses a family of random variables to reflect the influence of a typhoon on wave height at different times and then displays the statistical characteristics of wave height in time and space. At the same time, under the constraints of the given observations, the maximum uncertainty of the unobtainable data is maintained. The new model covers the compound extreme value distribution model that has been widely used and overcomes the subjective interference of the artificially selected distribution function—to a certain extent. Taking the typhoon wave height data of Naozhou Observatory as an example, this paper analyzes the probability of typhoon occurrence frequency at different times and the characteristics of typhoon intensity in different time periods. We then calculate the wave height return level and compare it with traditional calculation models. The calculation results show that the new model takes into account the time factor and the interaction between adjacent time periods. Furthermore, it reduces the subjective human interference, so the calculated results of the typhoon’s influence on wave height return level are more stable and accurate.
In the design of offshore platforms, the height of the bottom deck directly affects the safety and engineering cost of the entire platform. It is a very important scale parameter in platform ...planning. The American Petroleum Institute (API) specification shows that the key to determining the height of the bottom deck lies in the wave height and calculation of the return level of the water increase. Based on the perspective of stochastic processes, this paper constructs a new distribution function model for joint parameter estimation of the marine environment. The new model uses a family of random variables to show the statistical characteristics of design wave height and water increase in both time and space, with extreme value expanded EED-I type distribution used as marginal distribution. The new model performs statistical analysis on the measured hydrological data of the Naozhou Station during the flood period from 1990 to 2016. The Gumbel–Copula structure function is used as the connection function, and the compound distribution model of the wave height and the water increase is used to obtain the joint return level of the wave height and the water increase and through which the bottom deck height of the area is calculated. The results show that the stochastic compound distribution improves the issue of the high design value caused by simple superposition of univariate return levels. The EED-I type distribution still has good stability under the condition of less measured data. Thus, under the premise of ensuring the safety of the offshore platform, less measured data can still be used to calculate the height of the bottom deck more accurately.
Most of the offshore projects will be impacted by storm surge, especially in the sea area where typhoons are frequent, and storm surge disasters are inevitable. The establishment of a theoretical ...distribution model of the number of typhoon occurrences and random waves is of great theoretical and practical significance for the study of the number of storm surge impacts and damage to marine engineering as well as the safety evaluation of offshore engineering. Based on stochastic process theory, this paper discusses the effects of the number of typhoon occurrences and typhoon intensity on wave displacement and water level by constructing a compound Poisson process model of typhoon frequency and typhoon intensity. The limitations of using typhoon intensity and wave height as random variables in the marine environment are improved. The average cumulative damage, reliability, and average service life of marine works were analyzed by marine works reliability analysis and a compound Poisson process of the number of storm surge impacts on marine works and the damage caused to marine works by each impact. The results show that the statistical theoretical model and reliability analysis of the storm surge hazard factors based on the stochastic process covers the original extreme value statistical distribution model, and can determine the parameters in the model according to different thresholds in line with the objective facts, and then deduce the design return level, while the deduced return level still has a certain degree of reliability in the case of short or missing data. Therefore, the stochastic process-based model of the imputed level of design parameters for the marine environment provides a new option for marine engineering design and risk management.
•Social services utilization may highlight patients at risk of prolonged time to completion of chemoradiation.•With support from the treating institution, more patients may be able to complete ...therapy in an appropriate time.•Time to completion of chemoradiation >56 days remains a predictor of shorter PFS and OS.
We aimed to evaluate how the need for social services programs is associated with outcomes amongst patients with cervical cancer undergoing chemoradiation with a single institution, retrospective analysis of patients from January 1, 2015-July 31, 2018. Demographic, clinical, and social services utilization data were collected. Descriptive statistics and Chi-squared tests were performed. Kaplan-Meier curves estimated progression free (PFS) and overall survival (OS).
Among 117 eligible patients, median household income was $45,782 ($19,771 – $96,222). There was no difference in stage among income cohorts. Uninsured/publically insured patients had a higher stage at diagnosis than those privately insured (p = 0.003). Patients used 0–5 assistance programs during treatment. 77.6% of low income versus 54.2% of high income patients utilized ≥1 program. Assistance with lodging was utilized more often in low than high income patients.
(36.2% vs 15.7%, p = 0.013). 58.3% of patients completed therapy in less than 56 days. Patients who completed therapy in >56 days utilized 1.44 social services while patients completing in ≤56 days used 1.06 (p = 0.102). Social security disability utilization trended towards completion times >56 days (p = 0.064). There was no difference in PFS or OS based on income or social services utilized.
Financial toxicities associated with therapy are not limited to uninsured/publically insured or low income patients as over 50% of high income patients utilized at least one service. Additionally, the trend towards significance between enrollment in disability and completion of chemoradiation >56 days may highlight a group of at risk patients who need additional support.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aerosolized prostacyclins are frequently used in patients with severe acute respiratory distress syndrome and refractory hypoxia. Previous studies have shown improvement in oxygenation with use of ...pulmonary vasodilators such as iloprost and epoprostenol; however, there is no head-to-head comparison between these agents.
To compare the effects of inhaled epoprostenol and inhaled iloprost in critically ill patients with refractory hypoxia.
We performed a retrospective cohort analysis of patients admitted to the ICUs at the University of Oklahoma Health Sciences Center between 2015 and 2018. Adult patients who received aerosolized epoprostenol or iloprost for more than 4 hours were included in the analysis.
The primary endpoint measured was to compare the change in Pao
/Fio
ratio between patients treated with iloprost compared with epoprostenol. Secondary outcomes measured were 90-day in-hospital mortality and improvement in vasopressor requirements.
A total of 126 patients were included in the study, 95 of whom received iloprost (75%) and 31 patients (25%) received epoprostenol. There were significant improvements in Pao
/Fio
ratio in both the iloprost and epoprostenol group. Patients in the epoprostenol group appeared to have a higher 90-day mortality compared with the iloprost group. However, our study was not powered to detect a mortality difference and this finding likely represents a sicker population in the epoprostenol group and prescription bias. The use of iloprost was associated with higher vasopressor requirements in the first 12 hours of administration, an association was not observed in the epoprostenol group.
In this retrospective cohort analysis, use of both pulmonary vasodilators was associated with similar improvement in gas exchange. The mortality difference observed likely represents difference in severity of illness. Further studies are needed to corroborate these findings.
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